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May 4th, 2015

Increased Mortality Risk Found With Digoxin

For more than 200 years physicians have been trying to figure out how and when to use digoxin. Although it has a narrow therapeutic window and potentially dangerous interactions with other drugs, it is endorsed by current guidelines and widely given to patients with heart failure (HF) and atrial fibrillation (AF). However, there have been no randomized trials in AF and only one trial, the famous DIG trial, in HF. In that trial digoxin had no impact on mortality but was found to help reduce the rate of hospitalization for HF.

Now researchers led by Stefan Hohnloser have performed a meta-analysis of 19 studies of digoxin, including more than 235,000 AF patients and 91,000 HF patients. With the exception of the randomized, placebo-controlled DIG study, all the studies were observational.

Overall, there was a 21% increase in the relative risk of death in people taking digoxin (HR 1.21, CI 1.07 – 1.38, p= 0.01). Separately, the increased risk was 29% in the AF population and 14% in the HF population. There were three studies that included both AF and HF patients. In these trials there was a 28% increase in mortality in the AF group but no significant effect in the HF group.

The authors write that their finding “calls for randomized trials of dose-adjusted digoxin therapy at least in CHF patients. Until such proper randomized controlled trials are being completed, digoxin should be used with great caution (including monitoring plasma levels), particularly when administered for rate control in AF.”

In a press release from the European Society of Cardiology, Hohnloser said that his “personal feeling is that the time of digoxin – particularly as a heart rate-controlling drug in AF – is over. But this needs to be tested in appropriately designed studies.”